Pharmacodynamic Evaluation of Switching From Ticagrelor to Prasugrel in Subjects With Stable Coronary Artery Disease

NCT01587651 | Completed Phase 4 Results

• 1 other identifier: CS747s-B-U4003
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a Phase 4, multicenter, open-label (blinded Pharmacodynamic PD results), randomized, 3-arm, parallel-design study of subjects with stable Coronary Artery Disease CAD. This study will compare the PD effect of prasugrel 10 mg QD (once-daily) maintenance dose with ticagrelor 90 mg BID (twice daily) maintenance dose in subjects with stable CAD who have previously received ticagrelor loading does (LD) and maintenance dose (MD)..

Conditions

Coronary Artery Disease

Keywords

CAD; prasugrel; ticagrelor; antiplatelet; thienopyridine; P2Y12 Inhibitors

Outcome Measures

Primary Outcomes (1)

• P2Y12 Reaction Units

  P2Y12 Reaction Units (PRU) measured by VerifyNow P2Y12 assay VerifyNow P2Y12 assay, developed by Accumetrics, Inc. (San Diego, CA, USA), has been approved by the FDA to assess clopidogrel response using whole blood in a point-of-care testing fashion. Platelet aggregation with this system is defined by PRU, with a higher PRU indicative of greater platelet aggregation, and a lower PRU indicative of inhibition.

  7 days after first randomized dose

Secondary Outcomes (5)

• P2Y12 Reaction Units

  2, 4, 24, 48 hours after first randomized dose

• Platelet Reactivity Index

  2, 4, 24, 48 hours, 7 days after first randomized dose

• PRU Percent Inhibition (Device-reported)

  2, 4, 24, 48 hours, 7 days after first randomized dose

• PRU Percent Inhibition (Calculated)

  2, 4, 24, 48 hours, 7 days after first randomized dose

• Percentage of Subjects With High On-treatment Platelet Reactivity

  2, 4, 24, 48 hours, 7 days after first randomized dose

Study Arms (3)

Prasugrel Maintenance Dose

EXPERIMENTAL

Prasugrel 10 mg QD MD

Drug: Prasugrel Maintenance Dose

Ticagrelor Maintenance Dose

ACTIVE COMPARATOR

Ticagrelor 90 mg twice-daily (BID) MD

Drug: Ticagrelor Maintenance Dose

Prasugrel Loading Dose

EXPERIMENTAL

Prasugrel 60mg Loading Dose (LD), followed by prasugrel 10mg once-daily (QD) Maintenance Dose (MD)

Drug: Prasugrel Loading Dose; Drug: Prasugrel Maintenance Dose

Interventions

Prasugrel Loading Dose DRUG

60mg given as six 10mg film coated tablets

Also known as: Effient

Prasugrel Loading Dose

Prasugrel Maintenance Dose DRUG

10mg maintenance dose, given as one 10mg film coated tablet

Also known as: Effient

Prasugrel Loading Dose; Prasugrel Maintenance Dose

Ticagrelor Maintenance Dose DRUG

one 90mg film coated tablet

Also known as: Brilinta

Ticagrelor Maintenance Dose

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; age \>= 18 and \< 75 years
• Weight \>= 60 kg
• Receiving low dose ASA (75 mg to 150 mg daily) for at least 7 days at the time of Visit 1 and able to continue the same regimen throughout the study
• Stable CAD. CAD is defined as any of the following:
• History of a positive stress test
• Previous coronary revascularization including percutaneous coronary intervention (PCI), stent, or coronary artery bypass graft (CABG)
• Angiographic demonstration of CAD (at least
• lesion \>= 50 percent)
• Presence of at least moderate plaque by computed tomography (CT) angiography
• Electron beam CT coronary artery calcification score \>= 100 Agatston units
• If female, may be enrolled if
• One of the following 3 criteria are met:
• Had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form (ICF)
• Post-menopausal for at least 1 year
• If of childbearing potential, will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy

You may not qualify if:

• Have a defined need for adenosine diphosphate (ADP)-receptor inhibitor therapy, such as any of the following (or any other condition that in the Investigator's judgment would require such therapy):
• Within =\< 12 months of an acute coronary syndrome (ACS) event (unstable angina \[UA\], non-ST-elevation myocardial infarction \[NSTEMI\], or ST-elevation myocardial infarction \[STEMI\]) regardless of initial treatment (that is, invasive versus noninvasive)
• Subjects who underwent angioplasty within 12 months including bare-metal stent and/or a drug-eluting stent
• Had any stent placed in an unprotected left main coronary artery or in the last patent artery within the last 12 months
• Received thienopyridine therapy within 30 days of study entry
• Plan to undergo coronary revascularization at any time during the trial
• Presence or history of any of the following: ischemic or hemorrhagic stroke; transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation, or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)
• History of refractory ventricular arrhythmias with an increased risk of bradycardic events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree atrioventricular (AV) block or bradycardic-related syncope)
• History or evidence of congestive heart failure (New York Heart Association Class III or above =\< 6 months before screening
• Severe hepatic impairment
• History of uric acid nephropathy
• Uncontrolled hypertension, or systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg at screening
• Severely impaired renal function (glomerular filtration rate \< 30 mL/minute) or on dialysis
• At risk for bleeding
• Taking prohibited medications

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Eli Lilly and Company: collaborator

Study Sites (13)

Univ. of Florida College Medicine

Jacksonville, Florida, 32209, United States

Location

Clinical Pharmacology Unit of Miami

Miami, Florida, 33014, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Sinai Center for Thrombosis Research

Baltimore, Maryland, 21215, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45212, United States

Location

Black Hills Cardiovascular Research

Rapid City, South Dakota, 57701, United States

Location

West Houston Area Clinical Trial Consultants

Houston, Texas, 77094, United States

Location

Cardiology Center of Houston

Katy, Texas, 77450, United States

Location

University Hospital of Wales

Heathpark, Cardiff, CF14 4XW, United Kingdom

Location

Bristol Heart Institute

Bristol, B52 8HW, United Kingdom

Location

University Hospital Leicester

Leicester, LE3 9QP, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Fred Lipkin
• Organization: Daiichi Sankyo Medical Affairs

flipkin@dsi.com

973-944-2216

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: April 30, 2012
• Study Start: March 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: January 9, 2019
• Results First Posted: April 29, 2014

Record last verified: 2014-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

GB (5); US (8)